辛伐他汀对链脲佐菌素诱导2型糖尿病大鼠血糖的影响  

Effect of Simvastatin on Glucose Homeostasis in Streptozotocin Induced Type 2 Diabetic Rats

作　　者：王璐璐[1,2] 逄曙光[1,2] 黄仙萍[2] 田玉玲[2] 王少莲[2] 王聪聪[1,2] 

机构地区：[1]山东大学医学院,山东济南250012 [2]山东大学附属济南市中心医院,山东济南250013

出　　处：《中山大学学报（医学科学版）》2013年第4期521-525,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81170771;81101183;81270175);山东省科技发展计划(2012GSF11803);济南市国际合作计划(201011008)

摘　　要：【目的】探讨辛伐他汀对链脲佐菌素(STZ)诱导2型糖尿病大鼠血糖的影响。【方法】选取100只Wistar雄性大鼠适应性喂养1周后随机分为4组,每组各25只。A组(正常对照组)普通饲料喂养4周后腹腔注射柠檬酸钠缓冲液;B组(糖尿病模型组)、C组(他汀早期诱导组)和D组(他汀晚期诱导组)高脂饲料喂养4周后一次腹腔注射STZ 35 mg/kg溶液建立2型糖尿病大鼠模型,C组在高脂饲料喂养的同时给予辛伐他汀10 mg/kg·d-1的剂量灌胃,D组在糖尿病模型建立后给予相同剂量辛伐他汀灌胃,B组在糖尿病模型建立后给予等量蒸馏水,成模后均连续观察4周。测定各组0、4和8周大鼠体质量、空腹血糖和血脂水平,并于第8周末行OGTT试验。【结果】在第4周末和第8周末,2型糖尿病大鼠与正常对照组大鼠相比,空腹血糖(FPG)水平均显著升高(P<0.05)、血清胰岛素(Ins)水平显著降低(P<0.05),差异有统计学意义;与糖尿病大鼠相比,第4周末他汀晚期诱导组轻微升高FPG和降低Ins(P>0.05)、他汀早期诱导组显著升高FPG和降低Ins(P<0.001)以及更容易诱导糖尿病大鼠模型的建立;第8周末他汀晚期诱导组FPG显著高于糖尿病模型组(P<0.05)。【结论】对高脂饲料喂养的大鼠进行辛伐他汀(10 mg/kg·d-1)早期诱导更容易引起胰岛β细胞功能的减退从而升高FPG和诱发糖尿病模型的建立;在糖尿病模型建立之后,对糖尿病大鼠进行他汀治疗可以引起FPG升高。[Objective] To investigate the effect of simvastatin on glucose homeostasis in streptozotocin induced type 2 diabetic rats. [Methods] 100 male Wistar rats were randomly divided into four groups. 25 control rats were fed with standard diet four weeks and were injected citrate buffered saline by a single intraperitoneal. Others were fed with high-fat diet for four weeks, then diabetes were induced by a single intraperitoneal injection of STZ at 35 mg/kg body weight in 0.1 M citrate buffered saline （PH 4.2） after an overnight fast. The early simvastatin induced diabetic rats were fed with simvastatin at a dose of 10 mg/kg, d-1 during the whole experiment; the late simvastatin induced diabetic rats were fed with simvastatin after diabetes rats were induced. We measured body weight, fasting plasma glucose （FPG）, serum insulin （Ins）, cholesterol （CHO）, high-density tipoprotein cholesterol （HDL-C）, and triglyceride （TG） after an overnight fast. [Results] The FPG were higher and the Ins were lower in diabetic rats when compared to normal control rats; the early simvastatin induced diabetic rats had a higher FPG and a lower Ins level compared to the diabetic rats and were more easily be induced to diabetes at the end of 4 weeks, FPG level of late simvastatin induced diabetic rats was increased compared with diabetic model rats after 8 weeks. [Conclusion] These data indicates that the early simvastatin induced diabetic rats may cause hyperglycemia by impairing the function of islet β cells and have an adverse effect on glucose homeostasis , especially on FPG level.

关 键 词：血糖代谢 辛伐他汀 STZ诱导2型糖尿病大鼠 

分 类 号：R587.1[医药卫生—内分泌]